title: Response prediction in chronic hepatitis C by assessment of IP-10 and IL28B-related single nucleotide polymorphisms.
abstract: BACKGROUND
  High baseline levels of IP-10 predict a slower first phase decline in HCV RNA and a poor outcome following interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms (SNPs) adjacent to IL28B predict spontaneous resolution of HCV infection and outcome of treatment among HCV genotype 1 infected patients.
  
  
  RESULTS
  In the present study, we correlated the occurrence of variants at three such SNPs (rs12979860, rs12980275, and rs8099917) with pretreatment plasma IP-10 and HCV RNA throughout therapy within a phase III treatment trial (HCV-DITTO) involving 253 Caucasian patients. The favorable SNP variants (CC, AA, and TT, respectively) were associated with lower baseline IP-10 (P = 0.02, P = 0.01, P = 0.04) and were less common among HCV genotype 1 infected patients than genotype 2/3 (P<0.0001, P<0.0001, and P = 0.01). Patients carrying favorable SNP genotypes had higher baseline viral load than those carrying unfavorable variants (P = 0.0013, P = 0.029, P = 0.0004 respectively). Among HCV genotype 1 infected carriers of the favorable C, A, or T alleles, IP-10 below 150 pg/mL significantly predicted a more pronounced reduction of HCV RNA from day 0 to 4 (first phase decline), which translated into increased rates of RVR (62%, 53%, and 39%) and SVR (85%, 76%, and 75% respectively) among homozygous carriers with baseline IP-10 below 150 pg/mL. In multivariate analyses of genotype 1-infected patients, baseline IP-10 and C genotype at rs12979860 independently predicted the first phase viral decline and RVR, which in turn independently predicted SVR.
  
  
  CONCLUSIONS
  Concomitant assessment of pretreatment IP-10 and IL28B-related SNPs augments the prediction of the first phase decline in HCV RNA, RVR, and final therapeutic outcome.
authors.affiliation: Department of Infectious Diseases/Virology, University of Gothenburg, Gothenburg, Sweden. martin.lagging@medfak.gu.se
authors.forename: Martin
authors.initials: M
authors.lastname: Lagging
authors.forename: Galia
authors.initials: G
authors.lastname: Askarieh
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bibert
authors.forename: Jonas
authors.initials: J
authors.lastname: Söderholm
authors.forename: Johan
authors.initials: J
authors.lastname: Westin
authors.forename: Magnus
authors.initials: M
authors.lastname: Lindh
authors.forename: Ana
authors.initials: A
authors.lastname: Romero
authors.forename: Gabriele
authors.initials: G
authors.lastname: Missale
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
authors.forename: Avidan U
authors.initials: AU
authors.lastname: Neumann
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.forename: Bart L
authors.initials: BL
authors.lastname: Haagmans
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bochud
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Hellstrand
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D019698:Hepatitis C, Chronic / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011379:Prognosis; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D011994:Recombinant Proteins; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D054316:Biomarkers, Pharmacological; D054357:Chemokine CXCL10; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; D011994:Recombinant Proteins; C114753:CXCL10 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda